Hepatitis C viral infection is a major health problem that leads to chronic liver disease, such as cirrhosis and hepatocellular carcinoma, in a substantial number of infected individuals. Current treatments for HCV infection include immunotherapy with recombinant interferon-α alone or in combination with the nucleoside analog ribavirin.
Several virally-encoded enzymes are putative targets for therapeutic intervention, including a metalloprotease (NS2-3), a serine protease (NS3, amino acid residues 1-180), a helicase (NS3, full length), an NS3 protease cofactor (NS4A), a membrane protein (NS4B), a zinc metalloprotein (NS5A) and an RNA-dependent RNA polymerase (NS5B).
Potential treatments for HCV infection has been discussed in the different references including C. Blasano, Recent Advances in Antiviral Agents: Established and Innovative Therapies for Viral Hepatitis, 8(4) MINI-REV. MED. CHEM. 307 (2008); Robert Rönn & Anja Sandstrom, New Developments in the Discovery of Agents to Treat Hepatitis C, 8 CURRENT TOPICS MED. CHEM. 533 (2008); Julie Sheldon et al., Novel protease and polymerase inhibitors for the treatment of hepatitis C virus infection, 16(8) EXPERT OPIN. INVESTIG. DRUGS 1171 (2007); and Raffaele De Francesco et al., Approaching a new era for hepatitis C virus therapy: inhibitors of the NS3-4A serine protease and the NS5B RNA-dependent RNA polymerase, 58 ANTIVIRAL RESEARCH 1 (2003).
There is a clear and long-felt need to develop effective therapeutics for treatment of HCV infection. Specifically, there is a need to develop compounds that are useful for treating HCV-infected patients and compounds that selectively inhibit HCV viral replication. Thus, there is a need for compounds that are effective inhibitors of the NS3 protease.